TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8299	25120;25121;25122	chr2:178718111;178718110;178718109	chr2:179582838;179582837;179582836
N2AB	7982	24169;24170;24171	chr2:178718111;178718110;178718109	chr2:179582838;179582837;179582836
N2A	7055	21388;21389;21390	chr2:178718111;178718110;178718109	chr2:179582838;179582837;179582836
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-68
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.1768
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
K/E	rs2077774413	None	0.998	D	0.482	0.688	0.660424939923	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
K/E	rs2077774413	None	0.998	D	0.482	0.688	0.660424939923	gnomAD-4.0.0	6.57255E-06	None	None	None	None	N	None	0	6.54536E-05	None	0	0	None	0	0	0	0	0
K/R	None	None	0.726	N	0.33	0.292	0.293502639404	gnomAD-4.0.0	1.36967E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79905E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
K/A	0.9556	likely_pathogenic	0.9848	pathogenic	-1.059	Destabilizing	1.0	D	0.565	neutral	None	None	None	None	N
K/C	0.9706	likely_pathogenic	0.9784	pathogenic	-1.116	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
K/D	0.9858	likely_pathogenic	0.9956	pathogenic	-0.407	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
K/E	0.8362	likely_pathogenic	0.9436	pathogenic	-0.233	Destabilizing	0.998	D	0.482	neutral	D	0.635752111	None	None	N
K/F	0.98	likely_pathogenic	0.9848	pathogenic	-0.706	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
K/G	0.9624	likely_pathogenic	0.988	pathogenic	-1.471	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
K/H	0.6403	likely_pathogenic	0.7266	pathogenic	-1.768	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
K/I	0.9326	likely_pathogenic	0.9687	pathogenic	0.044	Stabilizing	0.999	D	0.859	deleterious	D	0.539882142	None	None	N
K/L	0.8804	likely_pathogenic	0.935	pathogenic	0.044	Stabilizing	0.998	D	0.737	prob.delet.	None	None	None	None	N
K/M	0.8289	likely_pathogenic	0.9012	pathogenic	-0.058	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
K/N	0.951	likely_pathogenic	0.9808	pathogenic	-0.867	Destabilizing	1.0	D	0.703	prob.neutral	D	0.598575407	None	None	N
K/P	0.9951	likely_pathogenic	0.9986	pathogenic	-0.296	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
K/Q	0.4908	ambiguous	0.6686	pathogenic	-0.853	Destabilizing	0.999	D	0.692	prob.neutral	D	0.531501577	None	None	N
K/R	0.0978	likely_benign	0.1185	benign	-0.761	Destabilizing	0.726	D	0.33	neutral	N	0.513036562	None	None	N
K/S	0.9595	likely_pathogenic	0.9865	pathogenic	-1.645	Destabilizing	1.0	D	0.547	neutral	None	None	None	None	N
K/T	0.911	likely_pathogenic	0.9694	pathogenic	-1.23	Destabilizing	1.0	D	0.748	deleterious	D	0.534464092	None	None	N
K/V	0.9153	likely_pathogenic	0.9584	pathogenic	-0.296	Destabilizing	0.999	D	0.808	deleterious	None	None	None	None	N
K/W	0.9561	likely_pathogenic	0.9679	pathogenic	-0.54	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
K/Y	0.9288	likely_pathogenic	0.9426	pathogenic	-0.223	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.